Welsh Fire 165 for 3 (Matthews 65) beat Southern Brave161 for 4 (Mandhana 70*, Wyatt 67, Griffiths 2-26, Matthews 1-35) by four runs
Hayley Matthews ended Southern Brave's unbeaten home record with a magnificent individual performance as Welsh Fire claimed a four-run win.
Matthews struck an impressive 65 to propel Fire to 165 for 3 - their record score in The Hundred - before the West Indies international defended nine in the final set.
Danni Wyatt and Smriti Mandhana both scored half-centuries in the chase but it was not enough as the Brave's women's team lost at the Ageas Bowl for the first time since the competition began.
Sent in to bat by Anya Shrubsole, Welsh Fire immediately looked a different prospect to previous seasons and were full of intent from the start of their innings.
Matthews timed her first ball from Shrubsole through the covers and struck an array of impressive drives, sweeps, and punches as she raced to her fifty off just 26 balls, the quickest half-century in Welsh Fire history.
Fire captain and England star Tammy Beaumont joined in the fun in the final set of the powerplay, cutting loose and hitting Chloe Tryon for three boundaries.
The Fire had raced to 80 when Beaumont became the first wicket to fall, stumped off Georgia Adams' bowling.
The hard-hitting Laura Harris was promoted up the order to capitalise on the fast start, and she struck two enormous sixes to race to 20 off seven balls, before an incredible piece of fielding from Maia Bouchier with a direct-hit from the long-on boundary brought about her demise. Matthews finally fell for a fantastic 65 chipping a return catch back to Tryon.
Sarah Bryce and Georgia Elwiss rotated the strike well before finishing with a flurry in a partnership of 48 to bring the score to 165 for 3, only one run short of matching the record score in The Women's Hundred.
Mandhana and Wyatt seemed to relish the task of pulling off a record run chase, and were quickly into their work. Wyatt struck boundaries all around the ground, including two enormous sixes over the leg side, as she raced to a sublime half-century off just 31 balls.
Alex Griffiths brought the much-needed breakthrough for Fire, as Wyatt holed out on 67 to Matthews at long on to end a 96-run opening stand.
Mandhana then assumed the responsibility of leading the home charge and dominated the Fire bowling, not deterred by losing Bouchier who was smartly stumped by Bryce of Griffiths.
Mandhana accelerated to a classy half-century from 33 balls, and continued to score freely, finishing on a stylish 70 from just 42 deliveries. But she was unable to see enough of the strike late on and while Brave looked on course with nine required off the final-set of five balls, Matthews took centre stage.
Matthews had Tryon stumped off the first ball, and then limited Mandhana and Freya Kemp to just three singles off her remaining balls to secure a historic win for Welsh Fire.
